Biology and pathobiology of lipid droplets and their potential role in the protection of the organ of Corti

Highlights

• Lipid droplets (LDs) are cellular organelles.

• LDs are involved in the storage, release and metabolic process of lipids and proteins.

• LDs have a central role in human diseases ranging from obesity and diabetes to cancer.

• There is a clear relationship between LDs and inflammatory responses.

• LDs could contribute to the resolution phase of inflammatory processes in the cochlea.

Abstract

The current review article seeks to extend our understanding on the role of lipid droplets within the organ of Corti. In addition to presenting an overview of the current information about the origin, structure and function of lipid droplets we draw inferences from the collective body of knowledge about this cellular organelle to build a conceptual framework to better understanding their role in auditory function. This conceptual model considers that lipid droplets play a significant role in the synthesis, storage, and release of lipids and proteins for energetic use and/or modulating cell signaling pathways. We describe the role and mechanism by which LD play a role in human diseases, and we also review emerging data from our laboratory revealing the potential role of lipid droplets from Hensen cells in the auditory organ. We suggest that lipid droplets might help to develop rapidly and efficiently the resolution phase of inflammatory responses in the mammalian cochlea, preventing inflammatory damage of the delicate inner ear structures and, consequently, sensorineural hearing loss.

This article is part of a Special Issue entitled <IEB Kyoto>.

Introduction

The observation of intracellular lipids is old in the field of cell biology. However, the study of the organelle chiefly involved in its storage, known as lipid droplet (LD), has just recently gained significant attention by basic scientists, clinical investigators, practitioners from many medical disciplines, and pharmaceutical companies. Fundamental studies in the field of cell biology, biophysics, and biochemistry, in particular those performed during the last twenty-five years, have revealed that LDs are not only involved in the storage but also in the release and metabolic processing of lipids and proteins involved in a number of intra-cellular and multi-cellular mechanisms. This field of research has been galvanized by extensive biochemical investigations that revealed that LDs are not simple inclusions of fat, but they have a constitutive cohort of resident molecules, including simple and complex lipids, steroids, and proteins, involved in a variety of critical cellular functions (Brown, 2001, Cermelli et al., 2006, Martin and Parton, 2006). In fact, a large number of laboratories around the world are currently working on extending these fundamental observations. The conceptual framework emerging from these studies is that, at a subcellular level, some components are involved in the regulation of the structure and function of the LD itself while others perform functions integrated at either the cellular or the whole organism level. Another focus of intensive investigation seeks to test the hypothesis that the molecular composition of LDs varies among cells, and even inside a single cell, according to their contributions to the structure and function of the resident tissue. This line of investigation is providing clues to the type and complexity of the contributions of LDs to cell specialization.

The study of LDs is pushing the development of technology ahead. This is evident by the increase in the application of very sophisticated biochemical and biophysical methods as well as genetically engineered model organisms. The most transformational impetus for the advancement of this field, however, can be found in the current need of translating the knowledge from the laboratory to the clinic at a faster pace. For instance, one of the most rapidly growing cause for disease in USA, and in many places around the world, are those associated with fat accumulation, storage, metabolism, and its conversion to energy. At the organelle level, the management of fat begins with the function of the LDs in adipocytes. The obesity epidemic has endowed us with bodies that carry and recycle a large amount of fat, which in many cases has direct toxic effects. For instance, the accumulation of fat in LDs underlies the pathogenesis of NASH (Non-Alcoholic SteatoHepatitis), a liver disease which has become one of them most frequent cause of death in modern medical practice (Karagozian et al., 2014). It appears, that unbalanced lipid management by cells, leads to “lipoapoptosis”, with concomitant inflammation, fibrosis, and organ failure, a process further enhanced by various toxins, including some commonly used drugs (Anderson and Borlak, 2008).

A nascent but very promising area of investigation involves studies on the function and disfunction of LDs in other organs and cell populations, besides the liver and adipocytes. This research is guided by the hypothesis that LDs would play a role in the biology and pathobiology of every organ and cell population just like in liver and adipocytes. It is on this shore of the current research tide that our laboratory is actively investigating the potential contribution of LDs to maintaining the health of the auditory organ. We want to understand how these organelles and their component mediate or antagonize the effects of ototoxic agents, as well as whether and how they participate in the development of human diseases. Therefore, in the current article we review the existing knowledge in this field, highlight the most current research directions, and describe a useful paradigm that can help in better understanding the role of LDs in the biology and pathobiology of auditory diseases.